Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To systematically review the clinical efficacy of paroxetine plus olanzapine versus paroxetine alone among depression complicated with sleep disorder patients in China.Methods PubMed,Embase,Cochrane Library,CINAHL,SinoMed,CNKI,VIP,WanFang Data databases,SUMsearch and Google search engine were electronically searched to collect randomized controlled trials(RCTs)of paroxetine plus olanzapine versus paroxetine in the treatment of depression complicated with sleep disorder Chinese patients from inception to April 3,2023.Two researchers independently screened the literature,extracted data and evaluated the risk of bias of the included studies,and the Meta-analysis was then performed by using RevMan 5.3 software.Results A total of 70 RCTs involving 5 683 patients were included.The results of Meta-analysis showed that:(1)the total effective rate in experimental group was significantly higher than that of the control group(OR=5.98,95％CI 4.51 to 7.94,P＜0.001);(2)Pittsburgh sleep quality index scores after treatment in the first month(MD=-2.81,95％CI-3.24 to-2.38,P＜0.001),in 2 months(MD=-2.41,95％CI-3.13 to-1.70,P＜0.001),in 3 months(MD=-2.80,95％CI-3.18 to-2.42,P＜0.001)and in 6 months(MD=-1.65,95％CI-1.83 to-1.48,P＜0.001)in experimental group were significantly lower than the control group;(3)Hamilton depression scale scores after treatment in the first month(MD=-5.79,95％CI-6.63 to-4.95,P＜0.001),in 2 months(MD=-4.33,95％CI-5.45 to-3.21,P＜0.001),in 3 months(MD=-3.76,95％CI-4.17 to-3.34,P＜0.001)and in 6 months(MD=-3.38,95％CI-3.60 to-3.15,P＜0.001)in experimental group were significantly lower than the control group;(4)Hamilton anxiety scale scores in experimental group were significantly lower than the control group(MD=-3.47,95％CI-3.78 to-3.16,P＜0.001).Conclusion Current evidence shows that,compared with the paroxetine alone in the treatment of depression complicated with sleep disorder patients in China,paroxetine plus olanzapine can effectively increase patients'total effective rate of clinical treatment,improve the sleep quality and depression symptoms in 1 month,2 months,3 months and 6 months after treatment,and also reduce patients'anxiety.Due to limited quality and quantity of the included studies,more high-quality studies are required to verify above conclusions.

Objective:To explore changes of acid-base metabolism in the brain tissue of patients with chronic ischemic cerebrovascular disease (CICVD) using MRI amide proton transfer-weighted (APTw) imaging.Methods:This was a cross-sectional study. From January 2021 to July 2022, thirty-nine patients with CICVD at West China Hospital, Sichuan University were retrospectively included. All patients received CT perfusion (CTP) and APTw imaging. NeuBrainCARE brain perfusion software was used to analyze the impaired perfusion sites and measure the mean transit time (MTT) and time to peak (TTP). Standard spatial matching between CTP and APTw images was performed to measure the APTw values of the same sites. For comparison with normal tissue, APTw values were measured for normal-appearing white matter (NAWM) in the ipsilateral cerebral hemisphere, the contralateral cerebral hemisphere, and the ipsilateral cerebellar hemisphere in areas of impaired perfusion. ANOVA was used to compare the APTw values of impaired perfusion brain tissue, ipsilateral cerebral NAWM, contralateral cerebral NAWM, and ipsilateral cerebellar NAWM. The Bonferroni method was used to correct for multiple comparisons. Pearson correlation coefficient was used to analyze the correlation between APTw values and MTT and TTP in the cerebral tissue with impaired perfusion.Results:In 39 patients with CICVD, both the mean and minimum APTw values of cerebral tissue with impaired perfusion were significantly lower than those in the NAWM of the ipsilateral cerebral hemisphere, the contralateral cerebral hemisphere, and the ipsilateral cerebellar hemisphere ( P<0.001). In the NAWM of the cerebellar hemispheres with unimpaired perfusion, both the mean and minimum APTw values were significantly higher than those in the ipsilateral cerebral hemispheres and the contralateral cerebral hemisphere ( P<0.001). Correlation analysis showed that MTT was significantly negatively correlated with both the mean APTw and the minimum APTw ( r values were -0.90 and -0.82, P<0.001). TTP was significantly negatively correlated with both the mean APTw and the minimum APTw ( r values were -0.86 and -0.78, P<0.001). Conclusion:APTw value can reflect acidosis in cerebral tissue with impaired perfusion in patients with CICVD.

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.

Objective:To understand the genome sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and spike protein variations during different epidemic periods in Wuxi City.Methods:Nucleic acid was extracted from the nasopharyngeal swab samples of six local cases of coronavirus disease 2019 (COVID-19) (from January to February, 2020) and 13 imported cases of COVID-19 (from March to September, 2021) in Wuxi City, and the whole genome was amplified to construct the sequencing library. The second-generation sequencer was used for sequencing. The CLC Genomics Workbench (21 version) software was used to analyze the offline data with NC_045512.2 as the reference strain, and MEGA 7.0 software was used to construct the phylogenetic tree.Identification of type was conducted by Nextstrain typing method and phylogenetic assignment of named global outbreak lineages (Pangolin) typing method.Results:There were five subtypes in Nextstrain and seven subtypes in Pangolin of the nineteen patients with COVID-19. Compared with NC_045512.2, the median nucleotide mutation sites were 29 (range 0 to 42) and amino acid mutation sites were 20 (range 0 to 34). The six local and 13 imported cases had no common nucleotide mutation sites and were in different evolutionary branches. The sequences of the six local cases were highly homologous with the reference strain sequences (NC_045512.2) at the early stage of the pandemic, and the evolutionary distance was close to that of the reference strain. The 13 imported cases were obviously divided into three evolutionary branches (Alpha, Beta, Delta variant).The four Beta variants shared eight amino acid mutation sites in spike protein, and the two Alpha variants shared eight amino acid mutation sites in spike protein, and the seven Delta variants shared five amino acid mutation sites in spike protein.Conclusions:New mutations of SARS-CoV-2 are constantly emerging during the epidemic. The increase of the nucleotide sites number may result in the change of spike protein amino acid. Therefore, the whole-genome sequencing analysis plays an important role in the accurate tracing of epidemic origin and adjustment of prevention and control measures.

Objective:To analyze the frequency and characteristics of polymyositis (PM) in idiopathic inflammatory myopathy (IIM), and to investigate whether PM is over-diagnosed.Methods:Patients diagnosed as IIM according to the Bohan & Peter criteria of IIM hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2008 to 2019 were involved in the study. Definite PM (dPM) was defined as typical clinical and pathological features including elevated creatine kinase (CK) level, muscle weakness and muscle biopsy findings with endomysial CD8 + T cell infiltration and expression of MHC-1 on sarcolemma. Meanwhile, dermatomyositis (DM), anti-synthase syndrome(ASS), immune-mediated necrotic myopathy(IMNM), sporadic inclusion body myositis(sIBM) and other myopathies were excluded according to the new classification criteria of IIM subtypes respectively. Statistical analysis was performed using SPSS software 24.0. The Kruskal-Wallis test and χ2 test were used to compare the clinical characteristics between the dPM group and other IIM subtypes. Results:A total of 1 259 patients with IIM including 1 015 (80.6%) DM and 244(19.4%) PM were enrolled in this study. According to the strict definition of PM criteria, only 0.5% of patients (6/1 259) in IIM could be diagnosed as dPM. Most PM patients were IMNM and ASS according to the new IIM subtypes criteria, of which 48.0% (117/244) were IMNM and 32.0% (78/244) were ASS. 66.7%(4/6) of dPM patients were women. One complicated with RA, and one was dPM overlaped with systemic sclerosis. All of them had muscle weakness, mild elevation of CK level [611(391,1 451) U/L], and were myositis-specific autoantibodies negative. Except one dPM patients who did not receive immunoregulatory therapy due to chronic obstructive pulmonary disease, the others were administrated with low or medium dose prednisone combined with or without immunosuppressive agents. After a median follow-up of (38±26) months, the muscle strength of dPM patients were improved.Conclusion:dPM is a very rare clinical subtype of IIM. PM is an over-diagnosed entity in clinical practice. Patients with dPM have mild symptoms and good outcome.

Through reviewing domestic and foreign literature on augmentative and alternative communication in patients with motor neuron disease，this paper summarized the characteristics of communication disorders in patients with motor neuron disease，the effect caused by poor communication，as well as the application of augmentative and alternative communication. The purpose of this study is to provide an appropriate augmentative and alternative communication system for patients with motor neuron disease with communication disorders，so as to improve the quality of life of patients，improve negative psychological emotions，and reduce the burden of caregivers.

Objective:To investigate the level and changing trend of microparticles (MPs) in super-elderly infected patients, and explore its early warning effect on infection.Methods:The infected patients ≥ 85 years old admitted to the Second Medical Center of Chinese PLA General Hospital from December 2018 to March 2019 were selected as the observation group, and the healthy volunteers ≥ 85 years old in the same period were selected as the control group. Venous blood samples were collected at the 2nd hour, the 2nd day and the 7th day after fever, and the inflammatory markers such as white blood cell count (WBC), neutrophil percentage (NEUT), C-reactive protein (CRP) and procalcitonin (PCT) were measured. The levels of MPs were determined by flow cytometry. AnnexinⅤlabeled CD11b positive MPs (AnnexinⅤ +/CD11b + MPs) represented leukocyte microparticles (LMPs), and AnnexinⅤlabeled CD66b positive MPs (AnnexinⅤ +/CD66b + MPs) represented neutrophil microparticle (NMPs). The differences of each index at different time points between the two groups were compared, and the predictive value of each index to the infection of elderly patients was analyzed by receiver operating characteristic (ROC) curve. Results:A total of 38 subjects were enrolled, including 28 cases in the observation group and 10 cases in the control group. The levels of LMPs and NMPs in the observation group increased to the peak at the 2nd hour after fever, and were significantly higher than those in the control group [LMPs (cells/μL): 55.0 (28.8, 197.2) vs. 19.0 (13.5, 28.3), NMPs (cells/μL): 226.5 (123.3, 516.5) vs. 26.5 (22.0, 48.8), both P < 0.01]. With the control of the disease, LMPs and NMPs decreased gradually. The NMPs on the 2nd day was significantly lower than that at the 2nd hour of fever [cells/μL: 106.0 (40.0, 309.0) vs. 226.5 (123.3, 516.5), P < 0.05], and the LMPs and NMPs on the 7th day were significantly lower than those on the 2nd day [LMPs (cells/μL): 17.0 (12.5, 43.8) vs. 42.0 (13.0, 117.0), NMPs (cells/μL): 30.0 (15.8, 62.0) vs. 106.0 (40.0, 309.0), both P < 0.05]. There was no significant difference in the levels of LMPs and NMPs between the two groups on the 7th day. Among the inflammatory markers, the NEUT in the observation group was significantly higher than that in the control group at the 2nd hour of fever (0.70±0.09 vs. 0.59±0.04, P < 0.01), but there was no significant difference in WBC, CRP and PCT between the two groups. On the 2nd day, the inflammatory markers in the observation group reached the peak and were significantly higher than those in the control group [WBC (×10 9/L): 9.33±2.44 vs. 6.37±1.28, NEUT: 0.78±0.08 vs. 0.57±0.04, CRP (mg/L): 5.67±2.99 vs. 0.33±0.18, PCT (μg/L): 0.80±0.67 vs. 0.07±0.03, all P < 0.01]. On the 7th day, the inflammatory markers in the observation group decreased significantly, and there was no significant difference between the observation group and the control group. ROC curve analysis showed that the area under ROC curve (AUC) and 95% confidence interval (95% CI) of LMPs and NMPs on the day of fever were higher than those of WBC, NEUT, CRP and PCT [0.888 (0.763-1.000), 0.973 (0.931-1.000) vs. 0.679 (0.346-0.811), 0.829 (0.700-0.958), 0.607 (0.404-0.811), 0.554 (0.358-0.749)]. Conclusion:LMPs and NMPs are significantly increased in the early stage of fever, which can predict the incidence of infection in the super-elderly patients.